"FirefoxPortable.exe launcher version 2.7.7.0 has a single-instance bug. When Firefox is already open and an external program (e.g. QuiteRSS) tries to open a new link, it shows the error: 'Firefox is already running, but is not responding.' Version 2.6.0.0 works correctly with Firefox 149. Please fix the single-instance handling in 2.7.7.0."
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I just tested Firefox Portable 149 with opening up a file/url while it was already running and it worked without issue. Are you using multiple instances with the manual INI setting? If so, opening files/urls isn't compatible with that mode. It can't reliably be tracked whether a given profile is in use or not and it gets borked easily. This support was dropped a long time ago.
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