Refractory multi-principal element alloys (RMPEAs) could provide next-generation high temperature alloys, but their ductility and high temperature strength need significant improvement. Emulating superalloy γ-γ’ microstructures, RMPEAs combining a ductile BCC matrix with embedded B2 precipitates for strengthening could meet this goal. Two-phase BCC-B2 RMPEAs have recently been demonstrated, but the B2 phase typically exhibits insufficient thermodynamic stability for operating temperatures ≥1300 °C. Using high-throughput CALPHAD predictions, we screen across 3,500 potential BCC-B2 systems. Promising compositions are predicted for alloys combining Ru-based B2s with refractory BCC elements. A total of 20 such compositions were arc-melted to characterize their as-cast and heat-treated microstructures. In these alloys, the RuHf B2 exhibits exceptional stability beyond 1900 °C but cannot be solutionized. By contrast, RuTi does solutionize and reprecipitate between 1300 and 1900 °C, providing a robust thermal processing pathway. RuAl can be solutionized but also tends to form competing intermetallic phases. Altogether, Ru-B2 RMPEAs offer great design flexibility and surpass the stability and thermal processability of previously studied BCC-B2 refractory alloys.