Abstract: Objective To compare the efficacy and safety of FOLFOXIRI(folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) and FOLFOX(folinic acid, 5-fluorouracil and oxaliplatin) regimens on patients with hepatic metastasis from colorectal cancers after simultaneous resection. Methods We collected 60 patients with hepatic metastases from colorectal cancers who received simultaneous resection from January 2008 to July 2011. They were divided into two groups and received FOLFOXIRI or FOLFOX regimens. The incidence of adverse effects was recorded. The differences in 1-, 2-, 3-year disease-free survival(DFS) and overall survival(OS) were compared. The data was examined using Kaplan-Meier survival analysis. Results For 60 patients randomized to receive FLOFOXIRI or FOLFOX regimens, the adverse effects included leucopenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, liver and kidney function damage, neurotoxicity, oral mucositis and alopecia. FOLFOXIRI group had a higher incidence of leucopenia and diarrhea; other adverse effects were similar to FOLFOX group. The 1-, 2-, 3-year DFS rates of FOLFOXIRI group and FOLFOX group were 73.3%, 43.3%, 26.7% and 60%, 13.3%, 10% respectively, and there were significant differences in 2-, 3-year DFS(P=0.019, P=0.038); the 1-，2-，3-year OS were 86.7%, 73.3%, 36.7% and 83.3%, 50%, 13.3%, and there was a significant difference in 3-year OS(P=0.024). Conclusion FOLFOXIRI and FOLFOX chemotherapy regimens are safe and effective. FOLFOXIRI group has higher incidence of leucopenia, diarrhea and a better trend of long-term survival.