The present observational cohort study was designed to elucidate the efficacy and safety profile of bevacizumab or cetuximab with chemotherapy as the first-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Clinical data were collected from a single-center registry study where mCRC patients received first-line fluoropyrimidine-based chemotherapy combined with either bevacizumab (188 patients with KRAS wild-type or mutated tumors) or cetuximab (101 patients with KRAS wild-type tumors) between January 2009 and December 2013. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for estimating the prognostic and predictive values of clinicopathological characteristics. No statistically significant difference was observed between the bevacizumab and cetuximab groups in terms of median progression-free survival (PFS) (10.6 vs 8.7 months, P = 0.317), median overall survival (OS) (27.7 vs 28.3 months, P = 0.525), or overall response rate (43.1% vs 53.5%, P = 0.108). For the subset of patients with peritoneal dissemination, bevacizumab-based triplet appears to be superior to cetuximab-based triplet as measured by PFS (9.6 vs 6.1 months) and OS (26.3 vs 12.7 months), but not for patients without peritoneal dissemination (PFS, 10.6 vs 9.1 months; OS, 27.9 vs 30.7 months) (all unadjusted and adjusted interaction P < 0.05). Our study suggests that bevacizumab- or cetuximab-based regimens have similar effectiveness as first-line treatment of mCRC in Chinese population. Patients with peritoneal dissemination were likely to gain more benefit from bevacizumab than cetuximab treatment. Future prospective studies are required to further confirm these results.