All 35 pts were identified as BRAF/RAS wild-type, and 33 (94%) had left-sided colon cancer. The percentages of pts with second-line, third-line and ≥fourth-line previous treatments were 37%, 49%, and 14%, respectively. Thirty-four pts (97%) had received targeted therapies previously, including 29 (83%) with anti-EGFR therapy. By December 31, 2021, 2 pts had withdrawn from the study for personal reasons, and the remaining 33 were evaluated for efficacy. Twelve of the 33 (36.4%) pts achieved clinical partial remission and 14 (42.4%) achieved stable disease; disease progression occurred in 6 pts and 1 patient died. The ORR was 36.4% and the DCR was 78.8%. Tislelizumab plus cetuximab and irinotecan shows an encouraging clinical efficacy and tolerable safety in previously treated pts with RAS wide-type advanced colorectal cancer.