Background: Significant proportion of metastatic colorectal cancer (mCRC) patients receive systemic therapy beyond second line. This study aims to assess predictors of survival outcome in patients treated with TAS 102/bevacizumab compared to TAS102 alone beyond 2nd line. Methods: In this retrospective study, we assessed patients with mCRC treated with TAS102/bevacizumab or TAS102 alone beyond second line in 4 institutes in Saudi Arabia from January 2020 to December 2022. We checked progression-free survival (PFS) and overall survival (OS) of the study group and we assessed different parameters that may affect the survival outcomes. Results: We included 68 patients in this analysis (39 treated with TAS102/bevacizumab, 29 with TAS102 alone) with a median follow up of 20 months. Noteworthy, 39.7% of patients received treatment in third line (56.4% vs. 17.2%, respectively, p = 0.001) and 48.5% developed neutropenia with first cycle (51.3% vs. 44.8%, p = 0.59). Time from stage IV diagnosis to study treatment (TTAS102) was > 18 months in 56.4% vs. 44.8 %, respectively, p = 0.34. The two treatment arms were balanced for other parameters including site of primary tumour, tumour stage at diagnosis. Median PFS was significantly higher with TAS102/Bevacizumab compared to TAS102 alone (5 vs 3 months, HR = 0.59, 95% CI 0.35-0.98, p = 0.043). Similarly, median OS was significantly improved with TAS102/bevacizumab (15 vs 8 months, HR = 0.55, 95% CI: 0.30-0.98. p = 0.034). After adjustment of line of study treatment, TTAS102 and number of metastatic sites, PFS and OS were significantly improved with TAS102/bevacizumab compared to TAS102 alone (PFS: HR = 0.48, 95% CI: 0.26-0.89, p = 0.021), (OS: HR = 0.54, 95% CI: 0.26-0.91, p = 0.034). Survival outcomes were higher with TAS102/bevacizumab compared to TAS102 in patients with TTAS102 > 18 months (PFS: 5 vs. 3 months, HR = 0.27, 95% CI: 0.12-0.62, p = 0.002), (OS: 22 vs. 6 months, HR = 0.28, 95% CI: 0.11-0.68, p = 0.005) and in patients with neutropenia with first cycle (PFS: 6 vs 3 months, HR = 0.45, 95% CI: 0.21-0.98, p = 0.043), (OS: 26 vs 8 months, HR = 0.33, 95% CI: 0.13-0.81, p = 0. 0.016). No difference in survival outcomes in patients with TTAS102≤ 18 months and those with no neutropenia with first cycle. Conclusions: TAS102 with bevacizumab is associated with improved PFS and OS beyond 2nd line compared to TAS 102 alone especially in patients with longer TTAS102 and first cycle neutropenia.