Background: The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients., Patients and Methods: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance., Results: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6., Conclusions: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS., Gov Registration: NCT03422601; EudraCT Number: 2009-010384-16., Competing Interests: Disclosure FP reported receiving grants from Bristol-Myers and Squibb and HalioDx outside the submitted work; participation in Scientific Advisory Boards & Meetings for Bristol-Myers Squibb, Roche, Janssen, Merck, and Gilead. FP has patents associated with the immune prognostic biomarkers. TA reported participation in Scientific Advisory Boards & Meetings and receiving honoraria from Roche, Ventana, Sanofi, Bristol-Myers Squib, Clovis, MSD Oncology, Servier, Tesaro, Pierre Fabre, and HalioDx outside the submitted work. JT reported receiving honoraria from Merck, Roche, Amgen, Lilly, Sanofi, Sirtex, Servier, Baxalta, and Celgene; a consulting or advisory role for Roche, Merck KGaA, Amgen, Celgene, Lilly, Shire, Servier, and Sirtex; speakers' bureau for Servier, Amgen, Shire, Roche, Genentech, Sanofi, Merck, Lilly, and Sirtex. DV reported receiving honoraria from HalioDx, Janssen, and Celgene; a consulting or advisory role for Celgene, HalioDx, Janssen-Cilag, and Theradiag. CB reported receiving honoraria and consulting fees from Roche, and sat on advisory boards of Bayer, Sanofi, and Servier. CL reported a consulting or advisory role for Celgene; travel, accommodation, or expenses from Roche and Merck. JB reported receiving honoraria from Roche, Bristol-Myers Squibb, Astra-Zeneca, Boehringer Ingelheim, and MSD; a consulting or advisory role for Roche, Bristol-Myers Squibb, Astra-Zeneca, Boehringer Ingelheim, and MSD; travel, accommodations, expenses from Roche and Bristol-Myers Squibb. JD reported expert testimony for Roche; travel, accommodations, expenses from Hospira. PL-P reported personal fees from Amgen and Merck; a consultant role for Amgen, Boehringer Ingelheim, AstraZeneca, and Pfizer. FH is a HalioDx full time employee, co-founder, and shareholder. AC is a HalioDx full-time employee and Shareholder. JG is the co-founder and chairman of the scientific advisory board of HalioDx; reported receiving grants from Perkin-Elmer, IO Biotech, MedImmune, AstraZeneca, Imcheck Therapeutics, and Janssen; participates in scientific advisory boards of Bristol-Myers Squibb, MedImmune, AstraZeneca, Novartis, Definiens, Merck Serono, IO Biotech, ImmunID, NanoString, Illumina, Northwest Biotherapeutics, Actelion, Amgen, Kite Pharma, Merck, and MSD; is a consultant for Bristol-Myers Squibb, Roche, GSK, Compugen, Mologen, and Sanofi; also has patents associated with the immune prognostic biomarkers. J-FE reported receiving honoraria from Roche, GSK, MSD, Amgen, and HalioDx; also has patents associated with the immune prognostic biomarkers. JH, FM, RBJ, RF, AK, LM, and MS have declared no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)