Abstract: Objective To compare the clinical efficacy of modified CAPIRI regimen with the standard FOLFIRI regimen in the treatment of metastatic colorectal cancer and to analyze its safety. Methods Patients with metastatic colon cancer who failed treatment with the first-line FOLFOX regimen from January 2015 to January 2016 were randomly assigned to the modified CAPIRI group and the standard FOLFIRI group. The clinical efficacy and safety between the two groups were compared. Results There were no significant differences between the two groups in pre-treatment tumor markers, and quality of life scores. CEA, CA199 and AFP in the modified CAPIRI group and the standard FOLFIRI group were lower than before, but there was no significant difference between the groups(all P>0.05). The overall quality of life scores of patients in the modified CAPIRI group[(43.71±4.52)scores] after treatment were significantly higher than those in the standard FOLFIRI group[(40.09±3.96)scores, t=3.862, P<0.001]. The ORR and DCR(20.00%, 75.00%) of patients with modified CAPIRI(23.81%, 66.67%) were similar to those of the standard FOLFIRI group(χ²=0.174, 0.687; P=0.677, 0.408). The median OS and PFS in the modified CAPIRI group were similar to the standard FOLFIRI group(Log Rank χ²=0.621, 0.206; P=0.431, 0.650), but the total incidence of adverse reactions and drug withdrawal rate in the modified CAPIRI group(52.50%, 0.00%), which were significantly lower than those in the FOLFIRI group(76.19%, 9.52%; χ²=5.030, 4.005; P=0.025, 0.045). Conclusion The improved CAPIRI regimen is similar to the standard FOLFIRI regimen in the treatment of metastatic colon cancer, but with fewer adverse effects and better tolerance.