Background:Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer. This phase II study was conducted to evaluate the effcacy and safety of the combination of S?1, oxaliplatin, and leucovorin (SOL) in the treatment of Chinese patients with metastatic colorectal cancer (mCRC). Methods:Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin (85mg/m2) on day 1, oral S?1 twice daily (80–120mg per day) on day 1–7, and leucovorin twice daily (50mg per day) simultaneously with S?1, every 2weeks. Results and discussion:Forty patients were enrolled in our study. In total, 296 cycles of SOL were administered. The overall response rate was 50.0%. At a median follow?up of 27months, progression?free survival and overall survival were 7.0months (95% conifdence interval [CI] 6.0–10.6months) and 22.2months (95% CI 15.1–29.3months), respec?tively. The most common grade 3/4 non?hematological adverse events were diarrhea (n=8, 20.0%), nausea (n=3, 7.5%), and vomiting (n=3, 7.5%). The most common grade 3/4 hematological toxicities were thrombocytopenia (n=3, 7.5%), neutropenia (n=1, 2.5%), and abnormal alanine transaminase/aspartate transaminase levels (n=1, 2.5%). There was one treatment?related death. Conclusions:The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC. Trial registration: Clinical trial information: ChiCTR?TNRC?100000838.