Real-World Comparison of Trifluridine–Tipiracil with or Without Bevacizumab in Patients with Refractory Metastatic Colorectal Cancer

<b>Background/Objectives:</b> Patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy face limited treatment options. While trifluridine-tipiracil (FTD-TPI) and regorafenib have shown modest efficacy in prior clinical trials, recent data from the SUNLIGHT trial demonstrated that combining FTD-TPI with bevacizumab (FTD-TPI+BEV) may improve overall survival compared to FTD-TPI alone. However, supporting evidence from real-world populations remains scarce. <b>Methods</b>: This retrospective study assessed the real-world effectiveness and safety of FTD-TPI+BEV versus FTD-TPI monotherapy in patients with refractory mCRC treated at two institutions from June 2020 to October 2024. <b>Results</b>: A total of 106 patients were included, with 47 treated with FTD-TPI+BEV and 59 with FTD-TPI alone. Median progression-free survival (PFS) was significantly longer with FTD-TPI+BEV compared to FTD-TPI alone (4.1 vs. 2.1 months; HR = 0.56; <i>p</i> = 0.004), while median overall survival showed a non-significant trend favoring FTD-TPI+BEV (8.4 vs. 6.3 months; HR = 0.74; <i>p</i> = 0.189). The disease control rate was also significantly higher with FTD-TPI+BEV (59.6% vs. 25.4%, <i>p</i> = 0.001). Subgroup analyses showed consistent PFS benefits. Grade 3-5 adverse events occurred at comparable rates between groups. <b>Conclusions</b>: FTD-TPI+BEV may represent a preferred salvage treatment option for refractory mCRC.