One thing you can do is check the data Firefox gathered from the system for Word-related content types. I use the term content-types rather than file extensions because Firefox doesn't really care about file extensions. If the server doesn't specify a content type that matches up to one it has seen before, then it will not know what to do with the file.

You can check the Options page, Applications panel:

"3-bar" menu button (or Tools menu) > Options

In the left column, click Applications. It may take 10 seconds to build the list. Then scroll down to the Microsoft content types and see whether you can make a permanent change here. I'm attaching a screenshot to this post for reference.

Thanks for the quick reply, however, I can make permanent changes in the content types applet - with no effect on outcome; I'm still prompted to confirm the default selection.

Does this problem occur on all sites? For example, Does Firefox know how to automatically handle links to DOCX files on Microsoft's site?

Some sample links: windows site:microsoft.com filetype:docx - Google Search

Even on Microsoft sites, Firefox still prompts to select a default action

The mimeTypes.rdf file has been migrated to handlers.json in 55, so that explains why you can’t find it. Try removing handlers.json instead (when Firefox is closed.)

After closing browser, I deleted handlers.json. Still prompted to select default action after choosing desired app several times. Tried restarting machine to handling what was loaded in memory - same. Noticed handlers.json was rebuilt but options: applications: no longer stores selection. Opened the json file in notepad and noticed that it doesn't match some of the default settings in options:applications applet

Does the issue also occur in Firefox’s Safe Mode? And in a new profile? Basically both answers are required in order to rule out any external causes.

It’s obvious the file is not updated, and some add-ons are capable of interfering here. That said, is the file itself updated every time you change actions in the interface anyhow, according to its timestamp (despite that the changes are not honored)?

If I understood your suggestion, I restarted the browser in safe mode, then clicked on link to open docx file. It prompted to select default action (Microsoft Word) - noticed the do this automatically check box is now greyed out - the document opened. Closed doc and browser - reopened in safe mode clicked on doc link and is still asking me to select a default action. Also created a new profile with no changes

- Instead of launching Safe Mode, can you disable all add-ons manually, as well as switch to the default theme, and restart? - I suppose you also tried downloading the file as a first action in that new profile, and actually launched that profile? - Again, does the timestamp of the file change after editing any action?

Beyond that, the server can still be misconfigured (the greyed out checkbox is a lead), so I’m afraid you need to provide us with an affected link to proof this is a general issue, or to see what goes wrong if not.

I apologize, but I'm not sure what you are asking me to do....what link are you looking for?

I was referring to e.g. a docx file type when opening it from the web. Can you provide such a link? Did you also try the last suggestions?