Background: The benefit of adding Oxaliplatin to neoadjuvant chemoradiotherapy in Locally Advanced Rectal Cancer (LARC) patients remains controversial. The present study investigated whether induction chemotherapy (CapOX), 2 cycles of CapOX combined with standard radiation (Oxa-CRT) concurrently and consolidation chemotherapy (CapOX) could improve OS compared with standard treatment (nCRT) for locally advanced rectal cancer. Methods: We conducted this randomized, single center, open-label, phase III trial in China. Eligible patients were pathologically confirmed rectal adenocarcinoma, clinical T3-4 with or without regional N + and no sign of distance metastasis determined by pelvic MRI, chest and abdominal CT scan. All patients were randomly allocated to the experimental group: pelvic radiation of 50Gy/25 fractions with 4 cycles of oxaliplatin and capecitabine (1 cycle of CapOX (oxaliplatin: 130mg/m^2, cape: 1000mg/m², bid, Day 1 to Day 14) administrated before radiotherapy as induction chemotherapy, 2 cycles of CapOX (oxaliplatin: 100mg/m², cape: 1000mg/m², bid, Day 1 to Day 14) administrated concurrent with RT, and 1 cycle of CapOX (oxaliplatin: 130mg/m², cape: 1000mg/m², bid, Day 1 to Day 14) conducted as consolidation chemotherapy); or control group: radiation with capecitabine. The primary end point was OS. This trial was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT02031939). Results: From January 2014 to June 2020, 556 patients enrolled in this study (n=278 in both groups), and 536 patients were evaluable (269 in experimental group and 267 patients in control group). Surgery was performed in 235 patients (84.5%) in experimental group and 242 patients (87.1%) in control group. The pCR rates were 27.8% (75 in 269) and 19.4% in control group (52 in 267) (p = 0.025). 16 and 5 patients achieved clinical complete response (cCR) in experimental and control group, respectively. Grade 3-4 toxicities were recorded in 42 (21.8%) and 6 (5.1%) patients in experimental and control group. The most common grade 3-4 toxicities were leukopenia, thrombocytopenia and neutropenia. The overall surgical complication rate was not significantly different between two groups (12.1% vs. 11.9%). Conclusions: Four cycles of CapOX combined with RT in LARC significantly increased complete tumor response in Chinese patients with acceptable toxicities. Clinical trial information: NCT02031939.