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A novel tube-in-tube millireactor with multiholes jet and twist tapes was designed and investigated for its excellent mixing, low price, and industrialization prospects. The inner tube fluid jets into the annular space through six circular microholes with a diameter of 0.2 mm that are evenly drilled around the inner tube. This arrangement achieves good inlet dispersion. The annular reaction channel is modified by three types of twist tape, which facilitates fluid splitting, recombination, and swirling. A detailed computational study has been carried out on the millireactor to characterize flow using a verified and validated CFD model. Villermaux-Dushman reaction and impulse method residence time distribution were used to study both the micromixing and macromixing performance. The multiholes jet has excellent micro-mixing performance with a micro-mixing time of less than 1 ms, at Re > 350. The twist tapes effectively improve the macromixing so that a Pe > 100 is achieved in most of the range of Re 32 ~ 634. Local flow field visualization of the annular spaces with tapes is obtained by PIV - RIM, and the results align with the CFD model. Highlights: A novel tube-in-tube millireactor with multiholes jet and twist tapes was designed with excellent micromixing and narrow RTD. Micromixing time is less than 1ms, at Re > 350. Pe > 100 in most of the studied range, V = 6 ~ 240 ml/min. The local flow field was obtained by PIV-RIM under structure shading. The micromixing and differential pressure between inner and outer tube are determined by R e h o l e . [ABSTRACT FROM AUTHOR]