Background: CPGJ602 is a recombinant anti-EGFR human-mouse chimeric monoclonal antibody. CPGJ602 plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) may have efficacy in KRAS/NRAS/BRAF wild-type metastatic colorectal cancer. Methods: In this open-label, randomized trial, patients who had received no previous treatment were randomly assigned (2:2:1) to receive CPGJ60（325mg/m², q2w) plus mFOLFOX6 (biweekly group), CPGJ602 (400 mg/m ² initial dose followed by 250 mg/m² /week thereafter) plus mFOLFOX6 (weekly group) or cetuximab (400 mg/m² initial dose followed by 250 mg/m² /week thereafter) plus mFOLFOX6 (cetuximab group). All subjects received treatment up to 16 weeks. The primary endpoint was the best overall response (BOR) at 16 weeks. The second endpoints were DCR, DOR, PFS, safety. Results: As of Dec 30, 2021, 76 patients were enrolled (30 in biweekly group, 32 in weekly group and 14 in control group). The best overall response achieved at 16 weeks was 76.7% (23/30, 95% CI 60.3% - 92.0%),78.1% (25/32, 95% CI 62.5% - 92.5%) and 78.6% (11/14, 95% CI 49.2% - 95.3%) in the biweekly group, weekly group and cetuximab group, respectively. The confirmed overall response rate at 16 weeks was 60%(18/30), 71.9%(23/32) and 57.1%(8/14) in the biweekly group, weekly group and cetuximab group, respectively. The PFS rates at 16 weeks were 81.5% (95% CI 57.7% -92.6%), 96.8% (95% CI 79.2%-99.5%), 81.3% (95% CI 41.5%- 95.2%) in the biweekly group, weekly group and cetuximab group, respectively. The most common adverse events were a decreased neutrophil count (60%，78.1% and 71.4% in the biweekly group, weekly group and cetuximab group respectively), decreased white-cell count (53.3%, 78.1% and 71.4% respectively), decreased platelet count (40.0%, 40.6% and 42.9% respectively), and elevated serum aspartate aminotransferase (43.3%, 37.5% and 35.7% respectively). Conclusions: CPGJ602 plus mFOLFOX6 could be an option for KRAS/NRAS/BRAF wild-type metastatic colorectal cancer. Clinical trial information: NCT04466254.