〔Abstract〕 Objective To investigate the effect of bevacizumab combined with FOLFOX chemotherapy regimen on tumor marker levels in colorectal cancer (CRC) patients. Methods A total of 113 CRC patients admitted to Ganzhou People's Hospital from June 2021 to February 2022 were selected and randomly divided into a control group (57 cases) and an observation group (56 cases). The control group was treated with FOLFOX chemotherapy program, and the observation group was treated with bevacizumab on the basis of the control group. The clinical efficacy, tumor marker levels, vascular endothelial growth factor (VEGF) levels, Karnofsky behavioral status (KPS) score and Zubrod behavioral statu (ZPS) scores, and the occurrence of toxic side effects were compared between the two groups. Results The clinical efficacy rate of patients in the observation group was higher than that of the control group, and the difference was statistically significant (P < 0.05). After treatment, the levels of carcinoembryonic antigen (CEA), glycocalyx antigen (CA) 125 and CA199 in the two groups were lower than that before treatment, and these indexes in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). After treatment, the levels of VEGF in the two groups were lower than those before treatment, and the index in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). After treatment, the KPS score of the two groups of patients was higher than that before treatment, and the ZPS score was lower than that before treatment, and the observation group was better than that in the control group, the difference was statistically significant (P < 0.05). Comparing the incidence of toxic side effects between the two groups, the difference was not statistically significant (P > 0.05). Conclusion Bevacizumab combined with FOLFOX chemotherapy regimen is more effective in treating patients with CRC, which can reduce the levels of tumor markers and VEGF, improve the physical condition, and has better safety.