We present 10-year results of the phase Ⅲ FOWARC trial, which evaluated the efficacy of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with or without radiation compared with fluorouracil with radiation in patients with locally advanced rectal cancer. A total of 495 patients age 18-75 years with stage Ⅱ-Ⅲ rectal cancer were randomly assigned to three treatment arms: fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, or mFOLFOX6 alone, followed by surgery and adjuvant chemotherapy. With a median follow-up of 10 years, the 10-year disease-free survival (DFS) rates were 52.5%, 62.6%, and 60.5%, respectively (P = .56). The 10-year locoregional recurrence (LR) rates were 10.8%, 8.0%, and 9.6% (P = .57), and the 10-year overall survival (OS) rates were 65.9%, 72.3%, and 73.4% (P = .90). Subgroup analysis identified ypTNM stage as a significant prognostic factor for DFS, LR, and OS (P < .0001, P < .006, P < .0001, respectively). Patients achieving pathologic complete response had 10-year DFS, LR, and OS rates of 84.3%, 3.0%, and 92.4%, respectively. No significant difference was observed in long-term survival outcome between mFOLFOX6 with and without radiation and fluorouracil plus radiation. These results demonstrate that neoadjuvant mFOLFOX6 chemotherapy can be considered as a therapeutic option in LARC.