Background: Bevacizumab combined with chemotherapy has been shown to improve response rate and PFS in metastatic breast cancer. The aim of our study was to demonstrate decreased toxicity of metronomic chemotherapy/bevacizumab when compared to paclitaxel/bevacizumab. Methods: In this multicenter, randomized phase III trial, we compared bevacizumab (10 mg/kg i.v. q 2 weeks) with either paclitaxel (90 mg/m2) i.v. on days 1, 8, and 15 of a 4 week cycle (arm A) or daily oral capecitabine (3x500 mg) and cyclophosphamide (50 mg) (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. Primary endpoint was the incidence of grade 3–5 adverse events (AE): febrile neutropenia, infection, sensory and motor neuropathy, mucositis and hand-foot-syndrome. Secondary endpoints included: objective response (OR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), other adverse events (AEs), and quality of life (QoL). Results: Between September 2010 and December 2012, 147 patients were included at 22 centers in Switzerland, 73 in arm A and 74 in arm B. The incidence rates of primary endpoint events were 25% (18/71; 95% CI 15–35%) for arm A and 24% (16/68; 95% CI 13–34%) for arm B (p=0.96). Objective response rates were 58% (42/73; 95% CI 0.46–0.69) and 50% (37/74; 95% CI 0.39–0.61) in arms A and B, respectively (p=0.45). Median PFS was 10.3 months (95% CI 8.7–11.3) in arm A and 8.5 months (95% CI 6.5–11.9) in arm B, p=0.90; other secondary efficacy endpoints (DCR, OS) were not significantly different between the two arms. Less hair loss in arm B was the only clinically and statistically significant difference in QOL. Conclusions: This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3–5 AEs of metronomic bevacizumab, cyclophosphamide and capecitabine but the combination could be an active, convenient treatment in HER-2-negative metastatic breast cancer. Clinical trial information: NCT01131195.