Background: Bevacizumab (BEV) with fluoropyrimidine-containing chemotherapy is well-established for patients (pts) with mCRC. There is a need for reproducible, validated, inexpensive and accessible prognostic markers to aid in treatment selection. Pre-treatment levels of systemic inflammatory markers including the neutrophil to lymphocyte ratio (NLR) have been shown retrospectively to be prognostic in many tumors. This study aimed to prospectively evaluate the relationship between NLR and treatment outcomes in previously untreated mCRC pts receiving BEV-based therapy. Methods: ASCENT (NCT01588990) is an open-label, single arm, phase-IV, multi-center study. Pts received 1st-line BEV+XELOX or mFOLFOX6 in phase A (PhA) with planned continuation of BEV+FOLFIRI beyond 1st progression in phase B (PhB). Primary analysis: association of NLR with progression free survival (PFS). Secondary analyses: overall survival (OS) and safety. Sub-study: safety in pts with intact primary in situ (PIS) and resected primary tumor (RPT). Results: 128 pts started PhA; median age 63.5 years (range: 26-84), 70(55%) females, 51(40%) PIS, 71(56%) and 56(44%) were PS 0 and ≥ 1; respectively. 53(41%) pts entered PhB. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32(25%) pts having a baseline level > 5. The hazard ratio (HR) for PFS by NLR > 5 vs ≤5 was 1.4 (95% CI: 0.9-2.2; p = 1.01). Median PFS was 9.2 months (mo; 95% CI: 7.9-10.8) for PhA and 6.7 mo (95% CI: 3.0-8.2) for PhB. HR for OS based on baseline NLR > 5 vs ≤5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). Based on a multivariate model, the 12-month predicted OS probability for pts with PS 0, no metastatic liver disease and ≤ 3 sites of other metastatic disease, was 87% in pts with bNLR ≤ 5 and 79% in pts with bNLR > 5. Median OS was 25 mo (95% CI: 19.2-29.7) for the full analysis set and 14.9 mo for PhB. Treatment related toxicities were numerically and qualitatively consistent with prior experience. There were 4(3%) instances of GI perforation, of which, 3(6%) occurred in the PIS group. Conclusions: Consistent with previous studies, the trend was towards worse PFS and OS in pts with higher bNLR, but the association was not proven. Clinical trial information: NCT01588990