114 Background: Standard first- and second-line chemotherapy regimens for mCRC are FPD-based. In the phase 3 SUNLIGHT trial, the addition of BEV to FTD/TPI significantly improved overall survival (OS) compared with FTD/TPI alone in patients with mCRC who had received no more than two prior chemotherapy regimens. Here, we assessed the effect of timing of prior exposure to FPD on efficacy outcomes among patients treated in SUNLIGHT. Methods: In this post-hoc analysis, OS, progression-free survival (PFS), and disease control rate (DCR) were assessed in patients treated with FPD within 2 months of enrollment (<2 months FPD-free exposure) and patients who had not received FPD for ≥2 months prior to enrollment (≥2 months FPD-free exposure). Differences in OS between FTD/TPI + BEV and FTD/TPI alone were assessed in each subgroup. The Kaplan-Meier method and log-rank test were used to compare differences in OS/PFS; DCR was compared using Fisher's exact tests. The hazard ratio (HR) for OS was estimated using a Cox proportional hazards model. Results: Of 246 patients randomized to FTD/TPI + BEV, 79 had ≥2 months FPD-free exposure and 167 had <2 months FPD-free exposure. Median OS (95% CI) was 11.8 months (9.4–not estimable) for patients with ≥2 months FPD-free exposure and 10.5 months (8.6–11.3) for patients with <2 months FPD-free exposure ( P=0.095); median PFS was 6.7 months (4.6–7.5) and 5.2 months (4.2–5.7), respectively ( P=0.043). The DCR among patients treated with FTD/TPI + BEV was 79.8% for patients with ≥2 months FPD-free exposure and 64.7% for patients with <2 months FPD-free exposure, with a between-group difference of 15.1% (95% CI: 3.6%–26.5%; P=0.018). Of 246 patients randomized to FTD/TPI alone, 91 had ≥2 months FPD-free exposure and 155 had <2 months FPD-free exposure. Median OS was 9.3 months (6.7–10.9) and 6.8 months (6.0–7.8) for patients with ≥2 and <2 months FPD-free exposure, respectively ( P=0.106) and median PFS was 3.6 months (2.1–3.9) and 2.1 months (2.0–2.7) ( P=0.002). The between-group difference in the DCR was 13.8% (50.6% vs. 36.7% for ≥2 and <2 months FPD-free exposure; 95% CI: 1.0%–26.6%; P=0.044). Compared with FTD/TPI alone, FTD/TPI + BEV resulted in longer OS in both the ≥2-month (HR 0.61, 95% CI: 0.41–0.93) and <2-month (HR 0.59, 95% CI: 0.45–0.78) groups, respectively. Conclusions: Owing to imbalances between the ≥2- and <2-month FPD-free exposure groups, the data need to be interpreted with caution. However, with both FTD/TPI + BEV and FTD/TPI alone, OS, PFS, and DCR were numerically higher in patients with ≥2 months FPD-free exposure than in those with <2 months FU-free exposure, potentially reflecting the better prognosis of the former group. The survival benefits of adding BEV to FTD/TPI were maintained regardless of the timing of exposure to FPD prior to enrollment. Clinical trial information: NCT04737187 .