Background: According to the IDEA trial (Shi Q et al. ASCO 2017;LBA1), 6-month adjuvant chemotherapy should remain the standard in stage III T4 or N2 colon cancer. The relatively poor survival in this high-risk subgroup (3-year disease-free survival ([DFS] rate, 66%) and the potential synergistic efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (demonstrated in stage IV colon and pancreatic cancers) suggest FOLFIRINOX as a regimen of particular interest in this setting. Methods: This multicenter, international, phase III trial (NCT02967289) conducted in 47 centers in France and Canada, plans to include 640 patients, aged 18 to 70 years, ECOG performance status ≤1, within 42 days (start treatment, within 56 days) after curative-intent R0 surgical resection of a pT4N1 or pT1-4N2 colon adenocarcinoma. Patients are randomized (1:1; minimization method) between adjuvant mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m², and 5-FU 2.4 g/m²over 46 h) or mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m² then 2.4 g/m²over 46 h), every two weeks for 24 weeks (12 cycles). Patients will be followed up for 5 years after the end of adjuvant chemotherapy. A gain of 9% in 3-yr DFS (primary endpoint) is expected (74% in the experimental arm vs. 65% in the control arm; α, 5% [two-sided log-rank test]; 1-b, 80%). Secondary endpoints include 2-yr DFS, overall survival, and toxicity. Since April 2017, 49 patients have been enrolled to date (accrual period, 4 years). Clinical trial information: NCT02967289