Background: The WJOG 6210G trial demonstrated a similar efficacy between FOLFIRI plus Bev and FOLFIRI plus panitumumab (Pani) at 2nd-line treatment in pts with KRAS exon2 wild-type mCRC (Shitara K, et al, Cancer Sci 2016). Recently, angiogenesis biomarker studies of clinical trials have identified VEGF-D as a potential predictor for angiogenesis inhibitors in mCRC. We evaluated whether VEGF-D level are associated with clinical outcomes in the WJOG 6210G trial. Methods: Plasma samples which were collected at pre-treatment were analyzed. VEGF-D level in plasma was measured by means of magnetic bead panel (G & G SCIENCE CO., LTD.). The correlations of VEGF-D level with progression-free survival (PFS) and overall survival (OS) were evaluated by cox regression analyses. Results: Ninety-nine pts were evaluable for VEGF-D level (Bev, n = 51; Pani, n = 48) among 121 pts enrolled in the WJOG6210G. The median VEGF-D level was 441 pg/ml (range 60-1570). VEGF-D level was not affected by the period from last administration of 1st-line Bev to start of 2nd-line treatment. When the median VEGF-D level was adopted as cut-off value, pts with high VEGF-D achieved a shorter PFS and OS than pts with low VEGF-D in the Bev arm [HR: 0.58 (95%CI 0.32-1.07), p = 0.08; HR: 0.62 (95%CI 0.34-1.11), p = 0.10]. In pts with high VEGF-D, the Bev arm tended to have a shorter OS and PFS compared to Pani arm [median: 12.4 m vs. 17.5 m, HR: 1.58 (95%CI 0.87-2.88); median: 4.7 m vs. 5.5 m, HR: 1.31 (95%CI 0.72-2.40)]; whereas, comparable OS and PFS in pts with low VEGF-D [median: 18.9 m vs. 16.5 m, HR: 1.08 (95%CI 0.59-2.01); median: 5.9 m vs. 7.2 m, HR: 1.10 (95%CI 0.62-1.99)]. OS was stratified by VEGF-D level quartile, then OS of Bev arm in each quartile was compared with that of Pani arm (Table). Clinical trial information: UMIN000031621.Conclusions: Our study suggests clinically meaningful association between VEGF-D level and clinical outcomes in mCRC pts treated with 2nd-line FOLFIRI plus Bev.