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Background: FOLFOX (folinic acid, 5-fluorouracil and oxaliplatin) is the most commonly used chemotherapy regimen for the treatment of colorectal cancer. FOLFOX is administered in 14-day cycles, though toxicities frequently lead to unplanned delays. We report the incidence of unplanned delays among patients receiving FOLFOX and describe the reasons for delays. Methods: We conducted a retrospective analysis of patients receiving FOLFOX chemotherapy for colorectal cancer. Patients were treated at one of two tertiary cancer centers between January 2012 and April 2016. Cycles 2–6 were assessed for delays, and treatments were considered delayed when the interval from prior treatment was >18 days. Reasons for unplanned delays were categorized based on review of clinical records. Results: We identified 214 patients receiving FOLFOX as standard-of-care therapy. The median age was 59 years, and 55% were female. Of 961 evaluable treatment cycles, 124 (13%) had unplanned delays, and 92 of 214 patients (43%) had one or more unplanned delays in cycles 2–6. Cytopenias (neutropenia and/or thrombocytopenia) were the most common cause of unplanned delays, affecting 34% of patients and accounting for 74 of 124 unplanned delays (60%). Conclusions: Delays are common during FOLFOX chemotherapy, with 43% of patients having at least one unplanned delay prior to completing cycle 6. Neutropenia and thrombocytopenia were the leading causes of unplanned delays. Our findings justify the development of systematic approaches for preventing unplanned delays, such as standardized laboratory treatment criteria and/or proactive dose adjustment strategies.