This meta-analysis aims to evaluate chemotherapy with XELOX (capecitabine plus oxaliplatin) versus FOLFOX (fluorouracil plus oxaliplatin) as a treatment for metastatic colorectal cancer (mCRC) in terms of efficacy and safety. Only randomized controlled trials (RCTs) comparing XELOX versus FOLFOX were included. A total of 4,363 patients from eight RCTs were available for analysis. Pooled analysis revealed that there were no statistical differences between both arms in OS, and ORR. XELOX arm had a higher incidence of thrombocytopenia, hand-foot syndrome, and diarrhea, whereas neutropenia had a higher incidence in the FOLFOX group. For mCRC, the effect of XELOX is similar to FOLFOX.