Background: Bevacizumab combined with platinum-based chemotherapy has been established as a standard treatment option in the first-line setting for advanced nonsquamous non–small cell lung cancer (NSCLC). However, there have been no evidence-based studies to support the use of bevacizumab beyond disease progression in NSCLC patients receiving such treatment. Methods: WJOG 5910L was designed as a multicenter, open-label, randomized, phase II trial of docetaxel (60 mg/m²) versus docetaxel (60 mg/m²) plus bevacizumab (15 mg/kg) every 3 weeks in patients with recurrent or metastatic nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet. The primary end point was progression-free survival (PFS). Results: One hundred patients were randomly assigned to receive docetaxel (Doc, n = 50) or docetaxel plus bevacizumab (Doc+Bev n = 50). The median PFS was 4.4 months for the Doc+Bev group and 3.4 months for the Doc group, with a hazard ratio (HR) of 0.71 (95% confidence interval [CI], 0.47–1.09) and stratified log-rank P value of 0.058, which met the predefined value for statistical significance (P < 0.2). The median overall survival also tended to be longer in the Doc+Bev group (13.1 months; 95% CI, 10.6–21.4) than in the Doc group (11.0 months; 95% CI, 7.6–16.1), with a HR of 0.74 (95% CI, 0.46–1.19; stratified log-rank P = 0.11). Frequent adverse events of grade ≥ 3 included neutropenia (90% in the Doc+Bev group vs. 82% in the Doc group), leukopenia (64% vs. 52%, respectively), and febrile neutropenia (26% in both groups). There were two treatment-related deaths (one in each group). Conclusions: The addition of bevacizumab to docetaxel in the second-line setting shows promising efficacy with regard to PFS for patients with nonsquamous NSCLC whose disease has progressed while receiving bevacizumab plus a platinum-based doublet. The addition of bevacizumab was associated with a slight increase in toxicity, although the combination regimen was tolerable. Phase III studies of this combination are warranted. Clinical trial information: 000004715.