Abstract: Objective To explore the difference in the effectiveness of bevacizumab combined with FOLFIRI regimen for the treatment of microsatellite stable (MSS) type, advanced recurrent left-sided and right-sided colorectal cancer. Methods A total of 58 patients who were admitted to the Affiliated Hospital of Xuzhou Medical University from September 2018 to December 2021 due to MSS-type advanced recurrent left-sided and right-sided colorectal cancer and treated with first-line bevacizumab plus FOLFIRI regimen were selected, and their clinical data were retrospectively analyzed. Their clinical characteristics, overall survival time (OS), progression-free survival (PFS), disease control rate (DCR), objective remission rate (ORR), and 1- and 2-year survival rates were compared. Results The proportion of MSS-type advanced right-sided colorectal cancer patients with combined incomplete bowel obstruction was higher (P<0.05). MSS-type advanced right-sided colon cancer patients were more likely to have combined anemia and weight loss >5 kg than left-sided colorectal cancer patients (both P<0.05). The proportion of right-sided colon cancer patients with a maximum tumor diameter of ≥5 cm was higher than that of left-sided colorectal cancer patients (P<0.05). The proportion of male patients in left-sided colorectal cancer patients was lower than that of right-sided colon cancer patients (P<0.05). After treatment, both groups showed remarkable decreases in carcinoembryonic antigen (CEA) and glycan antigen 199 (CA199), compared with those before treatment (P<0.05). The proportion of patients who developed liver metastasis was higher in the right-sided colon cancer group than that in the left-sided colorectal cancer group (P<0.05). The ORR in the left-sided and the right-sided colorectal cancer groups was 14.8% and 29.0%, respectively (P>0.05), and the DCR was 74.1% and 87.1% (P>0.05), respectively. The 1- and 2-year survival rates were 92.6% and 81.4% in the left-sided colorectal cancer group and 83.8% and 61.3% in the right-sided colon cancer group, respectively (P<0.05). The left-sided colorectal cancer group presented better median PFS than the right-sided colon cancer group, with better prognosis (13.7 months vs 10.1 months, P<0.05). The median OS in the left-sided colorectal cancer group was also significantly better than that in the right-sided colon cancer group (35.3 months vs 27.2 months, P<0.05). Conclusions The application of bevacizumab plus FOLFIRI regimen for the treatment of patients with MSS-type advanced recurrent colorectal cancer brings about differences in clinical features, metastatic sites and survival between the left-sided and right -sided colorectal cancers.