Disclosed are a pharmaceutical composition for treating locally advanced mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) and use thereof. The pharmaceutical composition of the present disclosure includes mFOLFOX6, bevacizumab, and a PD-1 inhibitor. Experimental results show that, when the pharmaceutical composition is used to treat 18 locally advanced (T4N×MO) MSS CRC cases, major pathological remission (tumor regression exceeds 90%) is achieved in 14 cases and pathological complete remission (no residual tumor cells) is achieved in 10 cases; tumor marker levels are all lowered to normal levels; there is no fatal serious adverse event (SAE); and the pharmaceutical composition has prominent safety and efficacy. For locally advanced (T4N×MO) pMMR/MSS CRC patients, the pharmaceutical composition can be administered in combination to make a tumor regress, to improve an R0 resection rate and a pathological complete response (pCR) rate and avoid toxic and side effects of three-drug chemotherapy and concurrent chemoradiotherapy.