Refractory multi-element alloys (RMEA) with body-centered cubic (bcc) structure have been the object of much research over the last decade due to their high potential as candidate materials for high-temperature applications. Most of these alloys display a remarkable strength at temperatures above 1000 ˝C, which cannot be explained by the standard model of bcc plasticity dominated by thermally-activated screw dislocation motion. Recent research on Nb-Mo-Ta-W alloys points to a heightened role of edge dislocations during mechanical deformation, which is generally attributed to atomic-level chemical fluctuations in the material and their interactions with dislocation cores during slip. However, while this effect accounts for levels of strength that are much larger than what might be found in a pure metal, it is not sufficient to explain the high yield stress found at high temperature in Nb-Mo-Ta-W. In this work, we propose a new strengthening mechanism based on the existence of thermal super-jogs in edge dislocation lines that act as strong obstacles to dislocation motion, conferring an extra strength to the alloy that turns out to be in very good agreement with experimental measurements. The basis for the formation of these super-jogs is found in the unique properties of RMEA, which display vacancy formation energy distributions with tails that extend into negative values. This leads to spontaneous, i.e., athermal, vacancy formation at edge dislocation cores, which subsequently relax into atomic-sized super-jogs on the dislocation line. At the same time, these super-jogs can displace diffusively along the glide direction, relieving with their motion some of the extra stress, thus countering the hardening effect due to jog-pinning We implement these mechanisms into a specially-designed hybrid kinetic Monte Carlo/Discrete Dislocation Dynamics approach (kMC/DD) parameterized with vacancy formation and migration energy distributions obtained with machine-learning potentials designed specifically for the Nb-Mo-Ta-W system. The kMC module sets the timescale dictated by thermally-activated events, while the DD module relaxes the dislocation line configuration in between events in accordance with the applied stress. We find that the balance between super-jog pinning and superjog diffusion confers an extra strength to edge dislocations at intermediate-to-high temperatures that is in remarkable agreement with experimental measurements in equiatomic Nb-Mo-Ta-W and several other RMEA. We derive an analytical model based on the computational results that captures this improved understanding of plastic processes in these alloys and and explains the experimental data.